Thioxanthones are useful intermediates for the preparation of pharmaceuticals in the field of psychotherapeutics and are used as activators or sensitizers in the photopolymerisation of ethylenically unsaturated monomers.
Basically thioxanthones are formed by cyclisation of 2-phenylthiobenzoic acid derivatives. As described by Smiles, J. Chem. Soc. (1911), 99, 645, this reaction can be performed in one step, by reacting 2,2′-dithiodibenzoic acid with an aromatic compound in sulfuric acid. The main drawbacks of the process are that yields are poor at 40–60%, a large excess of sulfuric acid has to be used, after reaction a large amount of dilute sulfuric acid has to be regenerated or disposed of and sulfonated aromatics are major by-products.
For these reasons, 2-chlorothiobenzoyl chloride (CTBC) or derivatives thereof have been considered as an obvious choice for a Friedel-Crafts type reaction to form thioxanthones. This reaction is first disclosed in U.S. Pat. No. 4,101,558, where 2-chlorosulfenylbenzoyl- or 5-chloro-2-chlorosulfenylbenzoyl chloride are reacted with benzene, chlorobenzene or biphenyl to form thioxanthone, 4,7-chlorothioxanthone and 2,7-dichlorothioxanthone, 2- and 4-chlorothioxanthone and 7-chloro-2-phenylthioxanthone in the presence of aluminum chloride as catalyst. The 2-chlorosulfenylbenzoyl chloride and the aromatic substrate are mixed in a suitable solvent and aluminum chloride is added in portions, giving rise to product yields from 70–91%. Applicants performed experiments under the conditions disclosed in U.S. Pat. No. 4,101,558. CTBC and isopropyl benzene (cumene) in 1,2-dichloroethane (DCE) were reacted in the presence of aluminum chloride. The isomer content of isopropyl thioxanthone in the organic phase was found to be 70% of theory and 50% as isolated yield.
Bernard Belleau et al., Synth. Commun., (1983), 13, 977–984, have investigated different types of Lewis acids as catalyst to form thioxanthones from CTBC and benzene, ortho-/para-xylene or 1,4-dimethoxy substituted benzene. Tin(IV)chloride was found to be the most effective catalyst. The experimental section describes mixing CTBC in a chlorinated solvent with tin(IV) chloride, after which the substrate is added in one lot. An attempt to perform the Friedel-Crafts reaction under the conditions described by Bernard Belleau et al. failed as CTBC disproportionated with aluminum chloride in DCE.